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Targeted Brain Delivery of Rabies Virus Glycoprotein 29-Modified Deferoxamine-Loaded Nanoparticles Reverses Functional Deficits in Parkinsonian Mice
journal contribution
posted on 2018-04-04, 18:19 authored by Linhao You, Jing Wang, Tianqing Liu, Yinlong Zhang, Xuexiang Han, Ting Wang, Shanshan Guo, Tianyu Dong, Junchao Xu, Gregory J. Anderson, Qiang Liu, Yan-Zhong Chang, Xin Lou, Guangjun NieExcess iron deposition
in the brain often causes oxidative stress-related
damage and necrosis of dopaminergic neurons in the substantia nigra
and has been reported to be one of the major vulnerability factors
in Parkinson’s disease (PD). Iron chelation therapy using deferoxamine
(DFO) may inhibit this nigrostriatal degeneration and prevent the
progress of PD. However, DFO shows very short half-life in
vivo and hardly penetrates the blood brain barrier (BBB).
Hence, it is of great interest to develop DFO formulations for safe
and efficient intracerebral drug delivery. Herein, we report a polymeric
nanoparticle system modified with brain-targeting peptide rabies virus
glycoprotein (RVG) 29 that can intracerebrally deliver DFO. The nanoparticle
system penetrates the BBB possibly through specific receptor-mediated
endocytosis triggered by the RVG29 peptide. Administration of these
nanoparticles significantly decreased iron content and oxidative stress
levels in the substantia nigra and striatum of PD mice and effectively
reduced their dopaminergic neuron damage and as reversed their neurobehavioral
deficits, without causing any overt adverse effects in the brain or
other organs. This DFO-based nanoformulation holds great promise for
delivery of DFO into the brain and for realizing iron chelation therapy
in PD treatment.
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dopaminergic neuron damageiron chelation therapybrain-targeting peptide rabies virus glycoproteinPDIron chelation therapyTargeted Brain DeliveryRabies Virus Glycoprotein 29- Modified Deferoxamine-Loaded Nanoparticles Reverses Functional Deficitsnanoparticle systemBBBoxidative stress levelsDFOsubstantia nigrablood brain barrierRVG 29 peptideintracerebral drug delivery
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